1. Field of the Invention
The present invention concerns antitumor compounds. More particularly, the invention provides novel taxane derivatives, pharmaceutical compositions hereof, and their use as antitumor agents.
2. Background Art
Taxol.RTM. (paclitaxel) is a natural product extracted from the bark of Pacific yew trees, Taxus brevifolia. It has been shown to have excellent antitumor activity in in vivo animal models, and recent studies have elucidated its unique mode of action, which involves abnormal polymerization of tubulin and disruption of mitosis. It has been recently approved for the treatment of ovarian cancer; and studies involving breast, colon, and lung cancers have shown promising results. The results of paclitaxel clinical studies are reviewed in Rowinsky and Donehower, "The Clinical Pharmacology and Use of Antimicrotubule Agents in Cancer Chemotherapeutics" Pharmac. Ther., 52:35-84, 1991.
Recently, a semi-synthetic analog of paclitaxel named Taxotere.RTM. has also been found to have good antitumor activity in animal models. Taxotere.RTM. is also currently undergoing clinical trials in Europe and the United States. The structures of paclitaxel and Taxotere.RTM. are shown below along with the conventional numbering system of taxane molecules; such numbering system is also employed in this application. ##STR1##
Taxol.RTM.: R=Ph; R'=acetyl PA0 Taxotere.RTM.: R=t-butoxy; R'=hydrogen
The instant invention relates to a novel class of taxanes. More particularly they are 7-0 ethers of taxane derivatives.